1. Field of Invention
This invention relates to pyrrole derivatives, pharmaceutical compositions containing them and methods of using them to treat inflammation in mammals. More particularly this invention relates to antiinflammatory 2-halo-4,5-diarylpyrroles and certain intermediates for their preparation.
2. Prior Art
J. Szmuszkovicz et al, J. Med. Chem., 9, 527-36 (1966) describe the synthesis and biological activity of antiinflammatory indoles and the preparation of certain diarylpyrroles.
E. Aiello et al., J. Heterocycl. Chem., 19(4), 977-979 (1982), describe the synthesis of various monobromo-, monochloro- and monoiodopyrroles as potential pharmaceutical intermediates.
Cherkofsky in U.S. Pat. No. 4,267,184 discloses the preparation of diarylpyrroles and the use of 4,5-diaryl-2-(substitutedthio)pyrroles as antiinflammatories.
U.S. Pat. No. 4,326,881 discloses 4-chloro-3-(2,3-dichlorophenyl)pyrrole and its use as a fungicide.
Japanese published Patent Appln. No. JA-7242833-R discloses .beta.-trifluoromethylphenyl-4-halopyrroles with antibacterial activity.
Japanese published Patent Application No. J5-9078/153-A discloses 3-chloro-4-phenylpyrroles as intermediates for agrochemicals and bactericides.
Coassigned U.S. patent application Ser. No. 354,300, filed on Mar. 3, 1982, now abandoned, discloses antiinflammatory 2,3-diaryl-5-halothiophenes of the formula: ##STR6## where Y is F, Cl, Br or I; R.sub.1 and R.sub.2 are independently pyridyl or optionally substituted phenyl; and R.sub.3 is H or C.sub.1 -C.sub.2 alkyl.
Coassigned U.S. patent application Ser. No. 404,962, filed on Aug. 3, 1982, now U.S. Pat. No. 4,503,065, discloses antiinflammatory 4,5-diaryl-2-haloimidazoles of the formula: ##STR7## where Y is F, Cl or Br; R.sub.2 and R.sub.3 are pyridyl or substituted phenyl; and R.sub.1 is H, methyl or 1-ethoxyethyl.
There is a continuing need for safe and effective antiinflammatory agents. Inflammation is a disease process characterized by redness, fever, swelling, and pain. Arthritis, in its various forms, is the most prevalent, chronic, and severe of the inflammatory diseases. Traumatic injury and infection also involve inflammation, and antiinflammatory drugs are often used in their treatment. The usefulness of most commercial antiinflammatories is limited because of toxicity and adverse side effects. Many produce gastric irritation and other effects, such as changes in blood cells and the central nervous system. Adrenocortical steroids produce gastric irritation and suppression of normal adrenal function.
The present invention results from efforts to develop new antiarthritic compounds with good antiinflammatory activity and minimal side effects that could be more effective in treating arthritis than presently available drugs.